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Immunological Reaction (immunological + reaction)
Selected AbstractsHigh-dose immunoglobulines and extracorporeal photochemotherapy in the treatment of febrile ulceronecrotic Mucha-Habermann diseaseDERMATOLOGIC THERAPY, Issue 4 2010Federica Marenco ABSTRACT Febrile ulcero-necrotic Mucha-Habermann disease (FUMHD) is a rare subtype of pityriasis lichenoides et varioliformis acuta (only 41 cases described to date), characterized by an acute onset of ulcero-necrotic papules accompanied by high fever and severe constitutional symptoms. We report a case of a 23-year-old man with a steroid-resistant FUMHD treated by intravenous immunoglobulins (IVIG) combined with methotrexate. Only one case of FUMHD treated by IVIG has been reported to date in literature. Also in our case, IVIG proved to be effective in inducing a dramatic improvement of ulceration and in arresting the appearance of new lesions. Moreover, in our experience we decided to perform a maintenance treatment with extracorporeal photochemotherapy (ECP), to the best of our knowledge not previously used in the treatment of pityriasis lichenoides et varioliformis acuta. ECP, which involves extracorporeal exposure of peripheral blood mononuclear cells to photo-activated 8-methoxypsoralen, induces an immunological reaction against auto-reactive T cell clones, without immune-depression and thus could potentially be useful particularly in FUMHD avoiding the risk of an infective reactivation. [source] New developments in our understanding of acne pathogenesis and treatmentEXPERIMENTAL DERMATOLOGY, Issue 10 2009Ichiro Kurokawa Abstract:, Interest in sebaceous gland physiology and its diseases is rapidly increasing. We provide a summarized update of the current knowledge of the pathobiology of acne vulgaris and new treatment concepts that have emerged in the last 3 years (2005,2008). We have tried to answer questions arising from the exploration of sebaceous gland biology, hormonal factors, hyperkeratinization, role of bacteria, sebum, nutrition, cytokines and toll-like receptors (TLRs). Sebaceous glands play an important role as active participants in the innate immunity of the skin. They produce neuropeptides, excrete antimicrobial peptides and exhibit characteristics of stem cells. Androgens affect sebocytes and infundibular keratinocytes in a complex manner influencing cellular differentiation, proliferation, lipogenesis and comedogenesis. Retention hyperkeratosis in closed comedones and inflammatory papules is attributable to a disorder of terminal keratinocyte differentiation. Propionibacterium acnes, by acting on TLR-2, may stimulate the secretion of cytokines, such as interleukin (IL)-6 and IL-8 by follicular keratinocytes and IL-8 and -12 in macrophages, giving rise to inflammation. Certain P. acnes species may induce an immunological reaction by stimulating the production of sebocyte and keratinocyte antimicrobial peptides, which play an important role in the innate immunity of the follicle. Qualitative changes of sebum lipids induce alteration of keratinocyte differentiation and induce IL-1 secretion, contributing to the development of follicular hyperkeratosis. High glycemic load food and milk may induce increased tissue levels of 5,-dihydrotestosterone. These new aspects of acne pathogenesis lead to the considerations of possible customized therapeutic regimens. Current research is expected to lead to innovative treatments in the near future. [source] Mouse model for allogeneic immune reaction against fetus recapitulates human pre-eclampsiaJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 1 2008Haruki Nishizawa Abstract Aim:, We have previously demonstrated that mRNA expression and enzyme activity levels of placental indoleamine 2,3-dioxygenase (IDO), which degrades L-tryptophan and blocks the proliferation of T cells, are significantly low in patients with severe pre-eclampsia. From this observation, we hypothesized that induction of maternal allogeneic immune reaction by reduced IDO activity is one of the causes of pre-eclampsia. Methods:, To examine this hypothesis, we administered an IDO inhibitor to pregnant female mice carrying allogeneic concepti. Since administration of an IDO inhibitor to pregnant mice starting at E4.5 is already reported to cause allogeneic fetal rejection, we modified the regimen and started the administration at E6.5 when the fetus and placenta have already been established. Results:, Pregnant mice treated with an IDO inhibitor developed high blood pressure and proteinuria in addition to local circulation impairment in the placenta, which is analogous to the lesions that are characteristic of human pre-eclampsia. In contrast, pregnant mice carrying syngeneic concepti did not manifest such symptoms. Conclusions:, Our findings reveal a pivotal role for IDO activity in the etiology of pre-eclampsia. These data also lend support to the current hypothesis that pre-eclampsia is one of the possible manifestations of a maternal immunological reaction against an allogeneic fetus. [source] Preparation of nitrocellulose (NC) immuno-affinity membrane for purification of rAPC antibodyJOURNAL OF SEPARATION SCIENCE, JSS, Issue 6-7 2008Haixiang Sun Abstract In this study, recombinant allophycocyanin (rAPC) with a purity of 98% was transferred from a gel to a nitrocellulose (NC) membrane to develop a simple and efficient immuno-affinity membrane. Atomic force microscopy (AFM) was used to investigate the surface topography of the affinity membrane and its characterization indicated that rAPC easily forms trimers or hexamers on the membrane surface on use of the given transfer method. The hydrodynamic radius (Rh) of the rAPC aggregation was equal to 103 nm or 365 nm according to dynamic light scattering (DLS), which was in agreement with the result obtained by AFM. Based on the specific immunological reaction of antigen and antibody, anti-APC antibodies were purified from rabbit polyclonal serum in a single step. The amount of absorbed antibody was 5.79 mg/g membrane according to analysis by ELISA methods. The purity of antibodies was up to 98% according to SDS-PAGE. The adsorption-desorption cycle of rAPC was repeated six times using the same immuno-affinity membrane, and there was no significant loss in adsorption capacity. The method provides a novel and efficient immunological affinity membrane for the purification of antibodies. [source] Granuloma annulare possibly triggered by antitetanus vaccinationJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 5 2002C Baykal Abstract We report the case of a 6-year-old girl with granuloma annulare (GA) possibly related to antitetanus vaccinations. The first episode occurred 2 months after the girl had been vaccinated but the lesions were not located at the vaccination site. After 1 year of being free of lesions, she had a second episode unrelated to vaccination. After another 6-month lesion-free period, the girl was administered another antitetanus vaccination and a solitary lesion developed at the vaccination site within 3 days. A few lesions developed on her legs in the 2 months following the appearance of the initial plaque. The literature includes two reports of cases with papular lesions limited to the hepatitis B vaccination site, both histopathologically consistent with necrobiotic granuloma, but clinically not suggestive of GA. To the best of our knowledge, GA following antitetanus vaccination and occurring at the vaccination site has not been reported before. Either the trauma alone from the injection or a vaccine-induced immunological reaction might have triggered the necrobiosis of collagen through some unexplained mechanisms. [source] The disposition of free and niosomally encapsulated Rac-flurbiprofen in dairy bovinesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010E. O. CONFALONIERI Confalonieri, E. O., Soraci, A. L., Becaluba, M., Denzoin, L., Rodriguez, E., Riccio, B., Tapia, O. The disposition of free and niosomally encapsulated Rac-flurbiprofen in dairy bovines. J. vet. Pharmacol. Therap. 33, 9,14. Pharmacokinetic parameters were established for flurbiprofen (FBP) after intravenous (i.v.) administration (0.5 mg/kg) of niosomal and nonniosomal formulations in dairy cattle. Niosomes of FBP showed a drug loading of 92.0 ± 0.7% and the intravenous administration of the FBP niosomes to dairy cattle did not produce any immunological reaction associated to niosomal components. Niosomal FBP was slowly eliminated from plasma and mean residual time (MRT) and AUC0,t and t 1/2 values were significantly higher than those for non niosomal FBP formulations. The results presented in this study indicate that the long circulation of FBP niosomes offers a potential application for improving the pharmacokinetic parameters of short half-life drugs for clinical use. Niosomes offer new promising perspectives of drug delivery modules in bovine therapeutics. [source] Mature teratoma of the uterine cervix with lymphoid hyperplasiaPATHOLOGY INTERNATIONAL, Issue 5 2003Sung-chul Lim A rare case of an extragonadal teratoma, which occurred primarily in the uterus, is described. The tumor developed in the uterine cervix as a conventional cervical polyp, 3 months after an elective abortion in a 27-year-old woman. Microscopically, the solid 2.2 × 1.8 × 1.5 cm mass was a mature teratoma with exuberant lymphoid elements. It consisted of ectodermal, mesodermal and endodermal derivatives. The lymphoid elements may have been a lymphoid hyperplasia, a chronic inflammatory reaction or a component of the teratoma. However, as the lymphoid tissues had no spatial relation to the teratomatous components, the possibility of a teratomatous element was excluded. This could be regarded as a result of an immunological reaction to the tissues composing the tumor, rather than just a chronic inflammatory response because the lymphoid reaction was present in the tumor, the tumor,host interface and the perivascular areas. Because of the patient's history of an abortion and a lymphoid reaction, the possibility of fetal remnants implantation was raised, so DNA typing to compare the teratoma portion with a normal portion of the host was performed. We found the teratoma portions to be in accordance with that of the host, and hence ruled out fetal remnants implantation. This case showed that a mature teratoma of the uterine cervix may manifest as a feature of implanted fetal tissue. In addition, a real teratoma should be included in the differential diagnosis of uterine teratomatous lesion, even when detected in patients with a recent history of pregnancy and lymphoid hyperplasia. [source] The Etiological Role of Allogeneic Fetal Rejection in Pre-EclampsiaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2007Haruki Nishizawa Problem It has been demonstrated that allogeneic fetal rejection in normal pregnancy is prevented by placental indoleamine 2,3-dioxygenase (IDO). Further, an immunological etiology has been implicated in pre-eclampsia. Method of study We examined the differences in placental IDO activity between normal and pre-eclamptic pregnancies. Results IDO mRNA expression and enzyme activity levels in the placenta were low in patients with severe pre-eclampsia. The enzyme activity also inversely correlates with the blood pressure of the patients. In the placentas from severe pre-eclampsia, IDO immunoreactivity was low, whereas regional T-cell infiltration was observed reciprocally proportional to the IDO activity. Conclusion Our findings implicate a potential role for IDO activity and a maternal immunological reaction against an allogeneic fetus in the etiology of pre-eclampsia. [source] The cutaneous cellular infiltrate to stingray envenomization contains increased TIA+ cellsBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2000M. Germain Stingrays result in approximately 2000 stings annually in the U.S.A., and thus are one of the most important venomous marine animals. After envenomization, there is immediate, intense pain with subsequent oedema, cyanosis followed by local erythema and petechiae. Progressive local necrosis and ulceration is variable, sometimes leading to gangrene. To characterize the inflammatory infiltrate at the site of a stingray injury, we examined tissue obtained approximately 4 days after stingray envenomization. Routine histology and immunohistochemical stains for lymphoid markers, including CD3, CD4, CD8, CD20, KP-1 and TIA were performed, and demonstrated a central area of haemorrhagic necrosis with a surrounding infiltrate of lymphoid cells and eosinophils. Approximately one-third of the mononuclear cells were TIA+, and these cells appeared mainly to correspond to the cells which were CD3+ and CD4+. The inflammatory cells, including the lymphoid populations, suggest that an immunological reaction may contribute to the delayed healing of stingray injuries. [source] The presence of Propionibacterium spp. in the vitreous fluid of uveitis patients with sarcoidosisACTA OPHTHALMOLOGICA, Issue 3 2005Toru Yasuhara Abstract. Purpose:,An immunological reaction to a bacterial antigen, such as Mycobacterium tuberculosis or Propionibacterium spp., is suspected to be an initial mechanism in the disorder known as sarcoidosis. We investigated whether or not P. acnes, P. granulosum or M. tuberculosis are present in the vitreous fluid of eyes suffering from uveitis with sarcoidosis. Methods:,Using polymerase chain reaction, we analysed the presence of P. acnes, P. granulosum and/or M. tuberculosis DNA in vitreous samples taken from six eyes with sarcoidosis and six control eyes. Results:,Among the six uveitis eyes with sarcoidosis, we detected P. acnes DNA in two eyes, P. granulosum DNA in four eyes, and both P. acnes and P. granulosum DNA in one eye, but no Propionibacterium spp. in the control eyes. M. tuberculosis DNA was not present in any of the patient or control eyes. Conclusions:,This is the first report indicating the presence of Propionibacterium spp. and/or its DNA in the vitreous fluid of sarcoidic eyes with uveitis. This, therefore, supports the idea that Propionibacterium spp. are involved in the aetiology of uveitis in sarcoidosis. [source] A New Technique for Reconstruction of the Atrophied Narrow Alveolar Crest in the Maxilla Using Morselized Impacted Bone Allograft and Later Placement of Dental ImplantsCLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 2 2008Per Holmquist DDS ABSTRACT Background: In cases when the alveolar crest is too narrow to host an implant, lateral augmentation is required. The use of autogenous bone blocks harvested from the iliac crest is often demanded. One disadvantage is the associated patient morbidity. Purpose: The purpose of this study was to clinically and histologically evaluate the use of morselized impacted bone allograft, a novel technique for reconstruction of the narrow alveolar crest. Materials and Methods: Two patients with completely edentulous maxillae and one partially edentulous, with a mean age of 77 years (range 76,79 years) were included in the study. The alveolar crest width was <3 mm without possibility to place any implant. Bone grafts were taken from a bone bank in Gävle Hospital. Bone from the neck of femur heads was milled to produce bone chips. The milled bone was partially defatted by rinsing in 37°C saline solution. After compression of the graft pieces with a size of 15 mm (height), 30 mm (length), and 6 mm (width), they were then fit to adapt to the buccal surface of the atrophied alveolar crest. One piece was placed to the right and one to the left side of the midline. On both sides fibrin glue was used (Tisseel®, Baxter AG, Vienna, Austria) to stabilize the graft. After 6 months of graft healing, dental implants were placed, simultaneously biopsies were harvested and in one patient two oxidized microimplants were placed. At the time of abutment connection, microimplants were retrieved with surrounding bone for histology. Fixed screw-retained bridges were fabricated in mean of 7 months after implant surgery. Radiographs were taken before and after implant surgery and after 1 year of loading. Results: Sixteen implants with an oxidized surface were placed (TiUnite®, Nobel Biocare AB, Göteborg, Sweden). After 1 year of functional loading, all implants were clinically stable. The marginal bone loss was 1.4 mm (SD 0.3) after 1 year of loading. The histological examination showed resorption and subsequent bone formation on the allograft particles. There were no signs of inflammatory cell infiltration in conjunction with the allograft. The two microimplants showed bone formation directly on the implant surface. Conclusions: This study shows that morselized impacted bone allograft can be used to increase the width of the atrophied narrow alveolar crest as a good alternative to autogenous bone grafts in elderly patients. The histological examination of biopsies revealed a normal incorporation process and no signs of an immunological reaction. Further studies with larger samples are of important to be able to conclude if equal results can be obtained using morselized impacted bone allograft as for autogenous bone graft. [source] An epidemiological analysis of severe cases of the influenza A (H1N1) 2009 virus infection in JapanINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 4 2010Koji Wada Please cite this paper as: Wada et al. (2010). An epidemiological analysis of severe cases of the influenza A (H1N1) 2009 virus infection in Japan. Influenza and Other Respiratory Viruses 4(4), 179,186. Background, The age distribution of confirmed cases with influenza A (H1N1) 2009 has shifted toward children and young adults, in contrast to interpandemic influenza, because of the age specificities in immunological reactions and transmission characteristics. Objectives, Descriptive epidemiological analysis of severe cases in Japan was carried out to characterize the pandemic's impact and clinical features. Methods, First, demographic characteristics of hospitalized cases (n = 12 923), severe cases (n = 894) and fatal cases (n = 116) were examined. Second, individual records of the first 120 severe cases, including 23 deaths, were analyzed to examine potential associations of influenza death with demographic variables, medical treatment and underlying conditions. Among severe cases, we compared proportions of specific characteristics of survivors with those of fatal cases to identify predictors of death. Results, Age distribution of hospitalized cases shifted toward those aged <20 years; this was also the case for deaths without underlying medical conditions. Deaths in adults were mainly seen among those with underlying medical conditions, resulting in an increased risk of death as a function of age. According to individual records, the time from onset to death in Japan appeared rather short compared with that in other countries. Conclusion, The age specificity of severe cases and their underlying medical conditions were consistent with other countries. To identify predictors of death in influenza A (H1N1) 2009 patients, more detailed clinical characteristics need to be examined according to different age groups and types of manifestations, which should ideally include mild cases as subjects. [source] ANALYSIS OF THE SOLUBLE PROTEINS IN THREE SPECIES OF PARASITOIDS AND MOLECULAR CHARACTERISTICS OF YOLK PROTEIN IN PTEROMALUS PUPARUM,INSECT SCIENCE, Issue 4 2001SUN Meng Abstract The results both from PAGE and capillary electrophoresis indicated that there was a female specific protein i.e. vitellogenin (Vg) or vitellin (Vt) in the female wasp of Pteromalus puparum (Hymenoptera: Pteromalidae). While there was no difference in the electrophoresis graph between soluble proteins of the female whole body and those of the male one both in two bracoids (Hymenoptera: Braconidae), i.e. Cotesia plutellae and Macrocentrus linears. According to the graph of the gradient SDS-PAGE, it was clear that the Vg or Vt of P. puparum consisted of two subunits with approximate molecular weights, and their molecular weights were 74.4 and 52.8 KDa, respectively. Both immunological reactions between some main different tissues of the female wasps and the male whole body and the polyantibody against the Vt of this parasitoid, and the graph of the gradient SDS-PAGE including soluble proteins sampled separately from hemolymph, fat body and ovary of the female and the whole body of the male demonstrated that Vg existed both in female fat body and hemolymph, and Vt deposited in the ovary, not in the male, as well as the Vg was synthesized in the female fat body. [source] Lack of association between pro-inflammatory cytokine (IL-6, IL-8 and TNF-,) gene polymorphisms and Graves' diseaseINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2005R.-H. Chen Summary Graves' disease (GD) is a common, autoimmune disease involving the thyroid gland, and it has been previously suggested that pro-inflammatory cytokines are involved in the disease's pathogenesis. The aim of this study was to test whether the interleukin (IL)-6 gene promoter region, or tumour necrosis factor (TNF)-, or IL-8 gene 3,-untranslated region (3,-UTR) polymorphisms could provide useful genetic markers for an individual's susceptibility to GD. A normal control group of 60 healthy people and 95 patients featuring GD were examined. Polymerase chain reaction (PCR)-based restriction analysis was performed for the three gene polymorphisms using endonucleases BsrBI, NcoI and ApaLI, respectively. We found no significant difference between the frequencies of genotype and allelic variants for the IL-6 gene promoter (,572 G/C), the TNF-, gene promoter (,308 A/G) and the IL-8 gene 3,-UTR (2767 A/G) for GD patients and for normal controls. Cytokines are a large group of proteins that may elicit multiple effects upon immunological reactions. It still appears to be very worthwhile to continue to aggressively search for cytokine gene polymorphisms in order to predict the development of such disease. [source] Vaccination against the Old World screwworm fly (Chrysomya bezziana)PARASITE IMMUNOLOGY, Issue 11 2000Sukarsih Chrysomya bezziana is an endemic pest of livestock or a threat to livestock production in large areas of Africa, the Middle East, southern and south-east Asia and Australia. Its control is difficult. The feasibility of vaccinating against this pest has now been explored. In-vitro and in-vivo assays have been established. Using these assays, it has been shown that first instar larvae, third instar peritrophic membrane and cardia are all sources of material able to induce immunological reactions in sheep which lead to significant reductions in larval growth. In-vitro assays following vaccination with peritrophic membrane also show larval mortality. Taken together, these effects lead to an 82% reduction in the weight of recovered larvae in vitro and 45% reduction in vivo. Preliminary evidence suggests that the mechanism of protection may be complex. [source] UV-induced skin changes due to regular use of commercial sunbedsPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2002J. Ruegemer Background/aim: Increased pigmentation and thickening of the epidermis are the most important photoprotective skin reactions induced by ultraviolet (UV) radiation. The present study was designed to find out what changes are induced by regular use of commercial sunbeds twice weekly over a period of 6 weeks. Methods: The parameters analysed were skin pigmentation measured by chromametry, minimal erythema dose (MED) as a parameter of light sensitivity, epidermal thickening as determined by histology, induction of keratinocyte apoptosis as determined by TUNEL staining and antioxidant metabolism as measured by changes of cis - and trans -urocanic acid (UCA) content of the skin. Results: As expected, chromametry confirmed the clinically obvious increased skin pigmentation. However, no increase in MED was observed. In addition, neither epidermal thickening nor sunburn cells were seen. Significant detectable changes in proportion of the UCA isomer content of the UV-exposed skin were seen. The total UCA and cis -UCA content increased significantly between nearly all points of measurement. The amount of trans -UCA first decreased, then increased significantly between the different time points. Conclusion: Our data indicate that sunbed-induced tanning is non-protective, which has to be addressed for persons looking for this effect before planning a stay in a sunny climate. However, sunbed-induced tanning may influence immunological reactions. [source] Accelerator mass spectrometry offers new opportunities for microdosing of peptide and protein pharmaceuticalsRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 10 2010Mehran Salehpour Accelerator Mass Spectrometry (AMS) is an ultra-sensitive analytical method which has been instrumental in developing microdosing as a strategic tool in early drug development. Considerable data is available for AMS microdosing using typical pharmaceutical drugs with a molecular weight of a few hundred Daltons. The so-called biopharmaceuticals such as proteins offer interesting possibilities as drug candidates; however, experimental data for protein microdosing and AMS is scarce. The analysis of proteins in conjunction with early drug development and microdosing is overviewed and three case studies are presented on the topic. In the first case study AMS experimental data is presented, for the measured concentration of orally administered recombinant insulin in the blood stream of laboratory rabbits. Case study 2 concerns minimum sample size requirements. AMS samples normally require about 1,mg of carbon (10,µL of blood) which makes AMS analysis unsuitable in some applications due to the limited availability of samples such as human biopsies or DNA from specific cells. Experimental results are presented where the sample size requirements have been reduced by about two orders of magnitude. The third case study concerns low concentration studies. It is generally accepted that protein pharmaceuticals may be potentially more hazardous than smaller molecules because of immunological reactions. Therefore, future first-in-man microdosing studies might require even lower exposure concentrations than is feasible today, in order to increase the safety margin. This issue is discussed based on the current available analytical capabilities. Copyright © 2010 John Wiley & Sons, Ltd. [source] Expression of haptoglobin in human keratinocytes and Langerhans cellsBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005H. Wang Summary Background, Epidermal Langerhans cells (LCs) play an important role in cutaneous immunological reactions. Freshly obtained or intraepidermal LCs are incapable of activating autologous naive T cells. However, when they are cultured for 2,3 days, LCs are able to activate autologous T cells. It has been proposed that haptoglobin (Hp) is the inhibitor that prevents LC functional transformation in the skin. Abundant Hp has been found in the cytoplasm of epidermal LCs. However, the source of Hp in LCs has not been addressed. Objectives, To determine the expression of Hp in epidermal cells, and to provide evidence that there is a functional relationship between LCs and keratinocytes (KCs) through Hp. Methods, Normal human epidermal cells and HaCaT cells were used for detection of Hp mRNA by in situ hybridization and reverse transcription,polymerase chain reaction, and Hp protein by immunohistochemical staining, immunofluorescence counterstaining and Western blotting. Results, Hp mRNA was expressed in normal human KCs and HaCaT cells, but not in normal human epidermal LCs. Hp protein was detected by immunohistochemical staining and immunofluorescence counterstaining in CD1a+ epidermal dendritic cells (LCs), but not in KCs. Hp protein was weakly expressed by HaCaT cells. Conclusions, Hp mRNA is present in normal human KCs and HaCaT cells, suggesting that they have the potential to synthesize Hp protein. Normal human epidermal LCs are unable to synthesize Hp protein by themselves, although they have abundant Hp protein in their cytoplasm. It is likely that LCs acquire Hp through an exogenous pathway. [source] Phase I clinical trial using peptide vaccine for human vascular endothelial growth factor receptor 2 in combination with gemcitabine for patients with advanced pancreatic cancerCANCER SCIENCE, Issue 2 2010Motoki Miyazawa Vascular endothelial growth factor receptor 2 (VEGFR2) is an essential factor in tumor angiogenesis and in the growth of pancreatic cancer. Immunotherapy using epitope peptide for VEGFR2 (VEGFR2-169) that we identified previously is expected to improve the clinical outcome. Therefore, a phase I clinical trial combining of VEGFR2-169 with gemcitabine was conducted for patients with advanced pancreatic cancer. Patients with metastatic and unresectable pancreatic cancer were eligible for the trial. Gemcitabine was administered at a dose of 1000 mg/m2 on days 1, 8, and 15 in a 28-day cycle. The VEGFR2-169 peptide was subcutaneously injected weekly in a dose-escalation manner (doses of 0.5, 1, and 2 mg/body, six patients/one cohort). Safety and immunological parameters were assessed. No severe adverse effect of grade 4 or higher was observed. Of the 18 patients who completed at least one course of the treatment, 15 (83%) developed immunological reactions at the injection sites. Specific cytotoxic T lymphocytes (CTL) reacting to the VEGFR2-169 peptide were induced in 11 (61%) of the 18 patients. The disease control rate was 67%, and the median overall survival time was 8.7 months. This combination therapy for pancreatic cancer patients was tolerable at all doses. Peptide-specific CTL could be induced by the VEGFR2-169 peptide vaccine at a high rate, even in combination with gemcitabine. From an immunological point of view, the optimal dose for further clinical trials might be 2 mg/body or higher. This trial was registered with ClinicalTrial.gov (no. NCT 00622622). (Cancer Sci 2009) [source] | |||||||||||||||||||||||||